Lecture 12 - OTC Analgesics

Question 1

neurons that detect sensory information in the periphery

Answer 1

primary afferents

Question 2

primary afferents synapse onto _____ in the spinal cord which pass sensory information up to the brain

Answer 2

secondary afferents

Question 3

take motor commands from the brain and send them to the periphery

Answer 3

motor efferents

Question 4

pain is detected by a specific class of primary afferents called:

Answer 4

nociceptors

Question 5

detect many types of painful stimuli (thermal, mechanical, chemical, etc)

Answer 5

polymodal nociceptors

Question 6

where are nociceptors found?

Answer 6

nociceptors densely innervate every surface of our body

Question 7

different types of painful stimuli are detected by specific receptors expressed on:

Answer 7

polymodal nociceptors

Question 8

temperature sensitive ligand-gated ion channels

Answer 8

transient receptor potential (TRP) channels

Question 9

TRPM8 is activated at:

Answer 9

temperatures below 10 degrees

Question 10

TRPV1 is activated at:

Answer 10

temperatures above 43 degrees

Question 11

released from surrounding immune cells following tissue injury or infection

Answer 11

inflammatory molecules (ie: bradykinin, cytokines, prostaglandins)

Question 12

what is arachidonic acid?

Answer 12

a fatty acid present in phospholipids of cell membranes

Question 13

arachidonic acid is freed from the phospholipid molecule by:

Answer 13

the enzyme phospholipase A2

Question 14

a key inflammatory mediator

Answer 14

arachidonic acid

Question 15

the enzymes cyclooxygenase-1 and cyclooxygenase-2 metabolize arachidonic acid into:

Answer 15

prostaglandins (PG) and thromboxanes (Tx)

Question 16

what are some of the functions of prostaglandins and thromboxanes?

Answer 16

• inflammation
• body temperature regulation
• platlet aggregation
• renal function
• etc

Question 17

• potent vasodilator
• pyrogenic (fever)
• attract immune cells (leukotactic) and coordinate the immune response
• involved in producing gastric mucous
  these are all characteristics of:

Answer 17

prostaglandin E2 (PGE2)

Question 18

signals to platlets to form clots and causes vasoconstriction

Answer 18

thromboxane A2 (TXA2)

Question 19

true or false: expression of cyclooxygenase enzymes is tissue specific

Answer 19

true

Question 20

COX1 is primarily expressed in _____, whereas COX2 is expressed in _____

Answer 20

non-inflammatory cells, inflammatory cells

Question 21

enzyme activity is either _____ or _____

Answer 21

constitutive (always on), inducible (must be activated by stimulus)

Question 22

aspirin and other non-selective NSAIDs inhibit:

Answer 22

both COX1 and COX2

Question 23

what is the effect of inhibiting of COX1 and COX2?

Answer 23

• decreases prostaglandin production that inhibits inflammation and reduces pain
• supresses prostaglandin synthesis in the brain

Question 24

how does daily NSAID use help those at risk of a stroke or heart attack?

Answer 24

prevents platlet aggregation (particularly aspirin)

Question 25

most NSAIDs inhibit the ______ of the cyclooxygenase enzymes

Answer 25

catalytic site (where arachidonic acid binds)

Question 26

acetylsalicylic acid (aspirin) is an:

Answer 26

irreversible inhibitor (covalently binds to the catalytic site of COX1 and COX2)

Question 27

how is the long half-life of aspirin explained?

Answer 27

it is an irreversible inhibitor of COX1 and COX2, meaning it has to be broken down and new COX enzymes have to be used

Question 28

non-selective NSAIDs are associated with:

Answer 28

gastric toxicity (due to inhibition of COX1 enzymes in gastric mucosa)

Question 29

chronic use of NSAIDs can result in:

Answer 29

gastric ulceration, upper GI bleeding, and renal failure

Question 30

a highly efficacious non-selective NSAID recommended for short term use post-surgically; however, chronic use produces long term gastric issues

Answer 30

ketoralac

Question 31

to bypass the gastric toxicity, _____ have been developed

Answer 31

specific COX2 inhibitors

Question 32

certain COX2 inhibitors are also associated with higher risk of:

Answer 32

cardiovascular toxicity

Question 33

inhibits a third COX isoform (COX3) found most abundantly in the cerebral cortex

Answer 33

acetominophen

Question 34

an analgesic and antipyretic agent that lacks anti-inflammatory effects

Answer 34

acetominophen

Question 35

what was the first local anesthetic discovered?

Answer 35

cocaine

Question 36

German chemist, Albert Niemann, introduced cocaine as a:

Answer 36

topical anesthetic for ophthalmological surgery

Question 37

list examples of topical anesthetics that look like cocaine, but lack the addictive and toxic side effects

Answer 37

- procain - lidocaine - bupivicane

Question 38

most local anesthetics contain a:

Answer 38

hydrophobic (aromatic) moiety, a linker region (ester), and a substituted amine

Question 39

what portion of a topical anesthetic (synthetic cocaine substitutes) determines the pharmacological properties of the molecule?

Answer 39

the linker region

Question 40

local anesthetics bind to a specific site within the:

Answer 40

pore of sodium channels (block ion movement through the pore)

Question 41

the site of the Na+ channels at which local anesthetics bind to is only accessible:

Answer 41

intracellularly (anesthetics must cross the membrane)

Question 42

all neurons require sodium channels for action potential propogation. so, local anesthetics block:

Answer 42

all sensation and cause motor paralysis in the area

Question 43

local anesthetics have a higher affinity for:

Answer 43

the open conformation of the sodium channel (so they preferentially block active neurons)

Question 44

are the effects of local anesthetics reversible?

Answer 44

yes

Question 45

capsaicin is an agonist for:

Answer 45

the TRPV1 receptor

Question 46

initial application of capsaicin cream causes:

Answer 46

moderate burning pain

Question 47

chronic activation of TRPV1 receptors due to application of capsaicin cream leads to:

Answer 47

desensitization and loss of TRPV1 nociceptors, leading to analgesia